High-dose chemotherapy for breast cancer: Clinical advantages of autologous peripheral blood progenitor cells (PBPC) compared with autologous bone marrow transplantation (ABMT)

Abstract

Peripheral blood progenitor cell (PBPC) autografts have a number of advantages over autologous bone marrow transplantation (ABMT) as haematopoietic support after high-dose chemotherapy in patients with breast cancer. These may include less contamination by tumour cells, reduced morbidity and mortality and additional dose escalation of chemotherapy. A dose-escalation study is described using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) primed PBPC support and post-infusion filgrastim for patients with high-risk or metastatic breast cancer. The regimen involved the use of cyclophosphamide, thiotepa and carboplatin at five dose levels. The main problem to emerge was organ toxicity induced by chemotherapy or sepsis. Patients receiving higher levels of chemotherapy were therefore allocated or not to an additional regimen involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to inhibit tumour necrosis factor alpha (TNF-α) which is believed to be one of the principal mediators of chemotherapy-related organ toxicity. The incidence of bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower in patients receiving the 'anti-TNF' therapy. No toxic deaths were seen in those patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC support and 'anti-TNF' therapy therefore allows a substantial increase in chemotherapy dosage. Further studies with larger patient numbers are required to show whether this decreased toxicity also produces increased patient survival.